neurodegeneration

Adult mice don’t need the gene that, when mutated in humans, causes the inherited neurodegenerative disorder Huntington’s disease.Â The finding suggests that treatment strategies for Huntington’s that aim to shut off the huntingtin gene in adults — now in early clinical stages — could be safe.

How HD gene silencing is supposed to work. The Emory study didn’t test this approach directly, but the Emory studyÂ has implications for what types of side effects HD gene silencingÂ may have in humans. Image from HDBuzz.net via Creative Commons.

Huntington’s disease is caused by a gene encoding a toxic protein (mutant huntingtin) that causes brain cells to die. Symptoms commonly appear in mid-life and include uncontrolled movements, balance problems, mood swings and cognitive decline. A juvenile form of Huntington’s disease also can appear during the teenage years.

Researchers led by Xiao-Jiang Li, MD, PhD and Shihua Li, MD, at Emory University School of Medicine, used genetically engineered mice in which the huntingtin gene can be deleted, triggered only when the mice are given the drug tamoxifen. Note: these mice don’t produce toxic mutant huntingtin protein.

When the huntingtin gene is deleted at an age older than four months, these mice appeared to stay healthy, despite having lost their huntingtin genes in cells all over their bodies. They maintained their body weight and could complete tests of movement and grip strength as well as control mice.Â In contrast with adults, engineered mice younger than four months old whose huntingtin gene was deleted developed lethal pancreatitis.